Follistatin 315 98% [Peptide]

Description

What is Follistatin 315?

Follistatin 315 (FST-315) is a 315-amino acid glycoprotein isoform of human follistatin, encoded by the FST gene through alternative mRNA splicing. It is classified within the activin-binding protein family and functions as an extracellular ligand sequestrant for select members of the TGF-β superfamily most notably myostatin (GDF-8) and activin A. Unlike its closely related counterpart, Follistatin 344 (FST-344), which carries a C-terminal extension conferring strong heparan sulfate proteoglycan binding and tissue-surface localization, FST-315 lacks this high-affinity heparin-binding domain and is instead the predominant circulating serum isoform. This pharmacokinetic distinction makes FST-315 particularly relevant for research designs examining systemic, soluble ligand antagonism rather than localized cell-surface activity.

In research settings, FST-315 has been investigated in preclinical models and in vitro systems for its ability to bind myostatin and activin A with high affinity, thereby preventing engagement of their cognate receptors (ActRIIA/B, ALK4/5) and attenuating the downstream SMAD2/3 signaling cascade that restricts skeletal muscle hypertrophy and promotes protein catabolism. It has also been examined in the context of reproductive endocrinology, given follistatin’s well-characterized role in pituitary FSH regulation via activin A antagonism.

Follistatin 315 supplied by RCDbio is intended strictly for laboratory and research purposes. It is not approved by the Food and Drug Administration for use in this research-grade, non-pharmaceutical form. It is not a dietary supplement and is not intended for human consumption or therapeutic self-administration.

Chemical Properties

Property	Detail
Product Type	Recombinant Glycoprotein Peptide (FST Gene Product, Alternative Splice Isoform)
Product Name	Follistatin 315 (FST-315; FS315)
Application	Scientific / Research Use Only
CAS Number	No confirmed isoform-specific CAS number has been separately indexed for FST-315 in major public databases. UniProt entry P19883 (human FST) provides primary sequence and protein identity reference.
Molar Mass	~34.7 kDa (glycosylated form; variable 31–49 kDa range dependent on glycosylation state; recombinant non-glycosylated backbone ~33.5 kDa)
Sequence (315 aa)	GNCWLRQAKNGRCQVLYKTELSKEECCSTGRLSTSWTEEDVNDNTLFKWMIFNGGAPNCIPCKETCENVDCGPGKKCRMNKKNKPRCVCAPDCSNITWKGPVCGLDGKTYRNECALLKARCKEQPELEVQYQGRCKKTCRDVFCPGSSTCVVDQTNNAYCVTCNRICPEPASSEQYLCGNDGVTYSSACHLRKATCLLGRSIGLAYEGKCIKAKSCEDIQCTGGKKCLWDFKVGRGRCSLCDELCPDSKSDEPVCASDNATYASECAMKEAACSSGVLLEVKHSGSCNSISEDTEEEEEDEDQDYSFPISSILEW
IUPAC Name	Not individually indexed in PubChem for the processed 315-aa isoform; full-length follistatin IUPAC notation corresponds to a ~35 kDa multichain glycoprotein — see PubChem CID 178101631 for reference entry
Synonyms	Activin-Binding Protein; FSH-Suppressing Protein; FST; FST-315; FS315
Physical Form	Lyophilized white to off-white powder
Solubility	Reconstitute in sterile water, bacteriostatic water, or 0.1% acetic acid; do not use reducing-agent-containing buffers. BSA carrier (0.1%) recommended for dilute working solutions.
Storage (Lyophilized)	−20°C; sealed, light-protected container with desiccant
Storage (Reconstituted)	4°C; use within 48–72 hours; avoid freeze-thaw cycling; discard turbid or discolored solution
PubChem CID	178101631 (follistatin protein reference entry)
Purity	≥98% (HPLC verified, independent third-party laboratory analysis; COA available per batch)
WADA Status	Follistatin 315 is prohibited under the 2026 WADA Prohibited List, Category S4.3 (Activin Receptor IIB Inhibitors – Myostatin-binding proteins), where follistatin is explicitly named. Verify at GlobalDRO.com.  Researchers engaged in sport-adjacent studies should verify the current status at GlobalDRO.com before use.

How Does Follistatin 315 Work?

FST-315 functions as a high-affinity extracellular ligand trap, binding myostatin (GDF-8) and activin A before they can engage their cell-surface type I and type II serine-threonine kinase receptor complexes (ActRIIA/B coupled with ALK4 or ALK5). By sequestering these ligands in the extracellular space, FST-315 prevents receptor-mediated SMAD2/3 phosphorylation and the nuclear translocation of transcriptional repressor complexes that otherwise suppress anabolic gene programs in skeletal muscle cells.

Myostatin (GDF-8) Sequestration and SMAD2/3 Pathway Attenuation

Myostatin signals through ActRIIB, which transphosphorylates ALK4/ALK5; the resulting intracellular signal activates Smad2 and Smad3, which form a complex with Smad4 and translocate to the nucleus to suppress downstream effectors of muscle hypertrophy. FST-315 binds myostatin with high affinity (Kd in the low nanomolar range), sterically preventing ActRIIB engagement. In rodent in vivo models, genetic or pharmacological removal of this myostatin inhibitory brake has been associated with both skeletal muscle fiber hypertrophy and hyperplasia, with concomitant attenuation of SMAD2/3-driven transcriptional repression (Nakatani et al., 2008; Rodino-Klapac et al., 2009).

Activin A Antagonism and mTOR Disinhibition

Activin A signals through an overlapping receptor axis (ActRIIA/B + ALK4) to activate SMAD2/3-mediated inhibition of muscle protein synthesis. FST-315 binds activin A with somewhat higher affinity than FST-288 alone when expressed as the serum-circulating form, providing dual-ligand sequestration. In vitro studies in C2C12 myoblast preparations and rodent models have characterized that follistatin-mediated suppression of SMAD3 activity is associated with activation of Akt and mTOR signaling — key anabolic nodes governing protein synthesis and satellite cell activation — through a mechanism partially independent of myostatin inhibition (Winbanks et al., 2012).

FSH-Pituitary Axis Modulation via Activin A Antagonism

Follistatin was originally characterized from ovarian follicular fluid based on its capacity to suppress follicle-stimulating hormone (FSH) secretion from pituitary gonadotrophs. This effect is mediated by activin A antagonism at the pituitary level: FST-315-mediated activin A sequestration attenuates activin-driven FSH synthesis. In rodent and primate models, this constitutes an off-target consideration for follistatin-based research designs. Notably, the 10-fold lower affinity of FST-315 for activin A compared to the tissue-bound FST-288 isoform (Al-Zaidy et al., 2015) partially mitigates, but does not eliminate, this pituitary axis effect at circulating concentrations.

BMP Pathway Selectivity

In vitro luciferase reporter data using CAGA (SMAD2/3) and BRE (SMAD1/5/8) reporters indicate that FST-315 selectively inhibits the activin A/myostatin-driven SMAD2/3 axis without substantial engagement of the BMP-9/BMP-10-driven SMAD1/5/8 pathway at research-relevant concentrations. This selectivity profile distinguishes FST-315 from broader TGF-β antagonists and informs experimental design in studies examining pathway-specific versus pan-TGF-β signaling.

Key Research Findings

• Myostatin antagonism and muscle mass (rodent model): Transgenic expression of a follistatin-derived myostatin inhibitor in mdx mice produced increased skeletal muscle mass, hypertrophy, hyperplasia, and reduced dystrophic pathology; myostatin binding characterized at Kd ~12.3 nM. [Nakatani et al., 2008 — PMID 17893249]
  
• FST-315 as circulating product of FST344 transgene (nonhuman primate): AAV1-delivered FS344 in cynomolgus macaque quadriceps generated FST-315 as the circulating serum product; muscle fiber size increases of 15–36% were observed in treated animals with no adverse cardiac histopathology recorded. [Kota et al., 2009 — PMID 20368179]
  
• SMAD2/3 and mTOR pathway interdependence (in vitro / rodent): Follistatin-mediated inhibition of Smad3 activity was characterized as critical for Akt and mTOR activation in skeletal muscle cell preparations; muscle hypertrophy proceeded through mechanisms partially independent of myostatin alone. [Winbanks et al., 2012 — PMID 22645138]
  
• FST-315 selectivity for activin/myostatin SMAD2/3 axis (in vitro): Luciferase reporter assays in cell-based systems confirmed FST-315 binding inhibits SMAD2/3 (CAGA reporter) but not SMAD1/5/8 (BRE reporter) activation; Kd to myostatin confirmed at low nanomolar range; BMP-9 and BMP-10 binding not measurable. [Mendell et al., 2015 — PMID 25356958]
  
• Follistatin gene therapy in Becker muscular dystrophy (Phase 1/2a): AAV1.CMV.FS344 delivered to BMD patients by intramuscular quadriceps injection, generating FST-315 as the processed serum product; functional improvement observed in a small-cohort proof-of-principle clinical study. [Mendell et al., 2015 — PMID 25356958]
  

All findings listed above are derived from preclinical or in vitro data, or early-phase exploratory clinical gene-therapy work. No conclusions regarding human therapeutic efficacy of research-grade recombinant FST-315 peptide can be drawn from these observations. These findings do not constitute evidence of safety or efficacy for any human condition or organism.

Potential Research Applications of Follistatin 315

Myostatin Pathway Pharmacology and TGF-β Ligand Sequestration Studies

FST-315 serves as a reference ligand-trap protein for in vitro investigations of the myostatin (GDF-8) signaling axis. In SMAD reporter cell systems, binding-competition assays, and receptor-activation studies, FST-315 is employed to characterize the structural requirements for high-affinity TGF-β superfamily antagonism. Researchers investigating ActRIIA/B receptor occupancy, SMAD2/3 phosphorylation kinetics, and downstream effectors of muscle protein catabolism use FST-315 as a tool to define the extracellular checkpoint of this regulatory axis.

Skeletal Muscle Cell Biology and Satellite Cell Research

In vitro rodent and human myoblast preparations have used follistatin isoforms to examine the relationship between myostatin/activin A suppression and satellite cell activation, myoblast proliferation, and differentiation. FST-315, as the predominant circulating isoform, is employed in models examining how systemic rather than locally bound follistatin influences muscle progenitor cell activity. Outcomes measured in preclinical systems include changes in MyoD expression, myosin heavy chain isoform composition, and fiber cross-sectional area.

Muscle-Wasting Disease Modeling (Dystrophy, Atrophy, Cachexia)

Preclinical models of Duchenne and Becker muscular dystrophy (mdx murine models, nonhuman primate preparations) have used follistatin gene delivery and recombinant protein administration to characterize the potential of myostatin pathway inhibition in dystrophic phenotype modification. FST-315’s circulating profile makes it relevant to systemic disease model designs. Endpoints examined include muscle mass, fiber morphology, inflammatory infiltration, and functional grip strength measurements.

Reproductive Endocrinology and Activin-Inhibin Axis Research

Given FST-315’s documented activin A antagonism, it is investigated in pituitary gonadotroph cell models for its role in FSH regulation. In vitro assays examining activin-driven FSH gene expression, and in vivo rodent studies of the hypothalamic-pituitary-gonadal axis, use follistatin isoforms as pharmacological tools to dissect activin-dependent signaling from other modulators of reproductive hormone secretion.

These applications are observed in preclinical and in vitro contexts only and do not constitute claims of efficacy or safety in any organism.

Potential Side Effects of Follistatin 315

• Reproductive endocrine perturbation: Activin A antagonism by FST-315 is expected to suppress pituitary FSH secretion in rodent and primate in vivo models; FSH reduction and downstream effects on gonadal axis function were a documented concern in follistatin gene-therapy planning and constitute a primary off-target consideration in preclinical studies.
  
• Organ mass changes: In rodent in vivo studies, supraphysiological follistatin expression has been associated with dose-dependent increases in organ weights beyond skeletal muscle, attributable to broad TGF-β superfamily suppression; findings are not uniform across models and dose ranges.
  
• Cardiovascular monitoring considerations (primate): Nonhuman primate gene-delivery studies included cardiac histopathology assessment as a safety endpoint; no adverse cardiac findings were reported at the doses examined in the Kota et al. (2009) paradigm, though this represents a single study in healthy animals.
  
• Inflammatory response to recombinant protein: As a large glycoprotein (>34 kDa), recombinant FST-315 may elicit immune or inflammatory responses in in vivo delivery models; glycosylation state and host expression system may influence immunogenicity in preclinical preparations.
  
• Hepatic changes at high exposures: Systemic overexpression studies in rodents have noted hepatic changes at very high expression levels; this is consistent with broad TGF-β ligand suppression and is dose-dependent.
  

No human safety or tolerability data pertaining to research-grade Follistatin 315 have been established. These observations are derived from experimental systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Handling Precautions

Follistatin 315 should be handled exclusively by trained laboratory personnel operating under appropriate institutional biosafety guidelines. Minimum personal protective equipment (PPE): nitrile gloves, laboratory coat, and eye protection. Lyophilized powder handling should be performed with care to minimize aerosolization; reconstitution should be conducted without vigorous pipetting or vortexing that could generate aerosols or introduce mechanical shear that disrupts disulfide-dependent tertiary structure. Avoid contact with reducing agents (DTT, β-mercaptoethanol, TCEP) at all stages of handling, as these will disrupt the multiple disulfide bridges critical to FST-315 folding and biological activity. Reconstituted solutions should be aliquoted to avoid repeated freeze-thaw cycling.

Exposure Risks

Risk Tier: MODERATE

FST-315 is a pharmacologically active glycoprotein with well-characterized activity as a high-affinity extracellular antagonist of myostatin and activin A. At research-relevant concentrations, it is not acutely toxic in preclinical in vivo systems; however, systemic or sustained exposure in animal models may produce off-target effects including reproductive endocrine perturbation (FSH suppression via activin A antagonism) and dose-dependent organ mass changes consistent with broad TGF-β superfamily disinhibition. No acute lethality has been documented in published preclinical data at research-relevant exposures. Plasma half-life as a circulating protein has not been uniformly established for recombinant FST-315; as a large glycoprotein, clearance is expected to follow a multi-compartment model subject to proteolytic processing. No human safety data have been established for research-grade Follistatin 315. Researchers should exercise caution appropriate to handling a potent biologically active protein with documented reproductive axis activity.

Storage

• Lyophilized form: Store at −20°C; sealed, light-protected container with desiccant
• Reconstituted form: Store at 4°C; use within 48–72 hours of reconstitution
• Do not subject to repeated freeze-thaw cycles; each cycle risks progressive disruption of disulfide bond integrity and loss of folding-dependent binding activity
• Do not store in the presence of reducing agents
• Discard any reconstituted solution that appears turbid, discolored, or shows particulate matter

FAQs

Q: What is Follistatin 315 and what is it investigated for in research? A: Follistatin 315 (FST-315) is a 315-amino acid circulating glycoprotein isoform encoded by the FST gene. It is investigated in preclinical and in vitro research systems for its role as a high-affinity binding protein that sequesters myostatin (GDF-8) and activin A — both TGF-β superfamily ligands — thereby attenuating their downstream SMAD2/3 signaling cascades. Research has examined its potential relevance in skeletal muscle cell biology, muscle-wasting disease models, and reproductive endocrinology. It is not approved by the FDA for human use.

Q: What distinguishes Follistatin 315 from Follistatin 344? A: Both isoforms are encoded by the FST gene and inhibit myostatin and activin A. The key mechanistic distinction lies in tissue distribution: FST-344 contains a C-terminal extension that includes a heparan sulfate proteoglycan binding domain, causing it to localize to cell surfaces and remain tissue-bound. FST-315 lacks this strong heparin-binding affinity and is the predominant circulating form found in serum, making it relevant to research designs examining systemic ligand sequestration rather than localized tissue effects.

Q: What is the half-life of Follistatin 315 in preclinical models? A: Precise plasma half-life data for recombinant FST-315 in standard rodent models are not uniformly established in published literature. As the circulating serum isoform, FST-315 avoids rapid cell-surface sequestration associated with heparan sulfate proteoglycan binding — a mechanism that reduces bioavailability of more tissue-retentive isoforms. In gene-delivery studies in nonhuman primates, the expressed FST-315 product demonstrated sustained serum detectability over the experimental observation period. These parameters are derived from preclinical systems and do not represent human pharmacokinetic data.

Q: How should Follistatin 315 be stored to maintain stability? A: Lyophilized form: Store at −20°C in a sealed, light-protected container with desiccant. Reconstituted form: Store at 4°C; use within 48–72 hours. Avoid repeated freeze-thaw cycles, as FST-315 contains multiple disulfide bridges whose oxidative integrity is critical to folding and binding activity. Discard any reconstituted solution that appears turbid or shows visible particulate matter.

Q: What toxicity observations have been reported in preclinical studies of Follistatin 315? A: In nonhuman primate gene-delivery studies, AAV-mediated FST expression (producing circulating FST-315) showed no adverse cardiac histopathology at the doses examined (Kota et al., 2009). Rodent studies observed dose-dependent increases in organ weights consistent with off-target activin inhibition. Reproductive endocrine perturbation is a documented preclinical concern, as follistatin suppresses pituitary FSH secretion via activin A antagonism. No human safety or tolerability data pertaining to research-grade FST-315 have been established.

Q: What is Follistatin 315 typically reconstituted with in laboratory research? A: In laboratory practice, lyophilized FST-315 is typically reconstituted with sterile water for injection, bacteriostatic water (0.9% benzyl alcohol), or dilute acetic acid (0.1%), depending on the downstream assay system. Avoid reconstitution buffers containing reducing agents (e.g., DTT, β-mercaptoethanol, TCEP), which can disrupt the disulfide bonds critical to FST-315 tertiary structure. Protein-carrier supplementation (e.g., 0.1% BSA) is recommended for long-term aliquot stability. These notes are for laboratory handling guidance only.

Q: Does FST-315 also inhibit bone morphogenetic proteins (BMPs)? A: In vitro data indicate that FST-315 does not exhibit meaningful binding affinity for BMP-9 or BMP-10 at research-relevant concentrations, distinguishing its SMAD-pathway selectivity profile from broader TGF-β antagonists. Luciferase reporter assays examining SMAD2/3 (CAGA reporter) and SMAD1/5/8 (BRE reporter) activity have characterized FST-315 as preferentially inhibiting the activin/myostatin-driven SMAD2/3 axis without substantially engaging the BMP-driven SMAD1/5/8 pathway. These observations are derived from in vitro cell-based systems.

Related Research Compounds

GDF-8 (Myostatin) [Peptide] — The primary TGF-β superfamily ligand targeted by FST-315; GDF-8/myostatin peptide preparations are employed in receptor-binding studies, SMAD2/3 reporter assays, and myoblast differentiation models as the direct molecular counterpart to follistatin isoforms.

BPC-157 [Peptide] — A synthetic pentadecapeptide investigated in preclinical models for connective tissue and muscle regeneration via pathways including growth factor modulation; used alongside follistatin research in models examining muscle repair and fibrosis.

Humanin [Peptide] — A mitochondrial-derived peptide investigated in preclinical models for cytoprotective and metabolic signaling; examined in some skeletal muscle biology contexts alongside TGF-β family studies for its role in cellular stress response and protein homeostasis.

References

1. Nakatani M, Takehara Y, Sugino H, et al. Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice. FASEB J. 2008;22(2):477–489. https://pubmed.ncbi.nlm.nih.gov/17893249/
   
2. Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve. 2009;39(3):283–296. https://pubmed.ncbi.nlm.nih.gov/19208403/
   
3. Kota J, Handy CR, Haidet AM, et al. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med. 2009;1(6):6ra15. https://pubmed.ncbi.nlm.nih.gov/20368179/
   
4. Winbanks CE, Weeks KL, Thomson RE, et al. Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin. J Cell Biol. 2012;197(7):997–1008. https://pubmed.ncbi.nlm.nih.gov/22711699/
   
5. Mendell JR, Sahenk Z, Malik V, et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Mol Ther. 2015;23(1):192–201. https://pubmed.ncbi.nlm.nih.gov/25322757/
   

Disclaimer 

Follistatin 315 98% [Peptide] is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

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